MFF p.Thr229=
c.687C>T · VCV4703737
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.84 | GERP -4.6 |
| Overall | ||
| CADD | 0.431 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,810 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000621%
10/1,610,730 alleles · very rare
exomes 10/1,458,450 · genomes 0/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,810 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,372 |
| European (non-Finnish) | 0.00068% | 147,148 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MFF
- Protein
- p.Thr229=
- Coding
- c.687C>T
- MANE Select
- NM_001277062
- Type
- single nucleotide variant
- Location
- chr2:227355704 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74
Similar variants
- MFF p.Arg128Trp Uncertain significance ★★ ⚠ same type
- MFF p.Arg136Cys Uncertain significance ★★ ⚠ same type
- MFF p.Arg136His Uncertain significance ★★ ⚠ same type
- MFF p.Arg199His Uncertain significance ★★ ⚠ same type
- MFF p.Arg6Gln Uncertain significance ★★ ⚠ same type
- MFF p.Arg92His Uncertain significance ★★ ⚠ same type
- MFF p.Asp75Asn Uncertain significance ★★ ⚠ same type
- MFF p.Gln52His Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mff-p-thr229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown